The effects of postnatal malnutrition on aging and longevity have been the subject of extensive studies. In the proposed project we will study (in rats) the effect of prenatal (maternal) malnutrition on aging and longevity of her offspring, with particular reference to the aging of this offspring's brain, as compared with the aging in normally nourished animals. Following extensive experience in this laboratory, the effects of several kinds of prenatal malnutrition (maternal dietary restriction) will be studied separately: protein deficiency, deficiency of single essential amino acids, and glucose (calorie) deficiency. Malnutrition during specific parts of pregnancy will be also studied. Following our previous findings, the effects of malnutrition in one generation on aging in the next generation will be also studied. Brain (cerebral) parameters to be studied at various ages to assess brain senescence include: cerebral wet and dry weight (water content), cortical thickness, cortical area, neuron packing density, neuron/glia ratio, neuronal perikarion size, dendritic tree (Golgi-Cox), total cerebral DNA (cell number) and protein, intracellular accumulation of lipofuscin; some of these determinations will be made for various regions of the brain. Some animals prior to sacrificing will be subjected to behavioral studies, in another attempt to assess the senescence of our prenatally malnourished animals as compared with the normal animals. Autopsy will be performed in order to ascertain the type and severity of age-associated organic diseases.